VOLTAGE-DEPENDENT FACILITATION OF A NEURONAL ALPHA(1C) L-TYPE CALCIUM-CHANNEL

Calcium entry into excitable cells through voltage-gated calcium chann els can be influenced by both the rate and pattern of action potential s. We report here that a cloned neuronal alpha(1C) L-type calcium chan nel can be facilitated by positive pre-depolarization. Both calcium an d barium were effective as charge carriers in eliciting voltage-depend ent facilitation. The induction of facilitation was shown to be indepe ndent of intracellular calcium levels, G-protein interaction and the l evel of phosphatase activity. Facilitation was reduced by the injectio n of inhibitors of protein kinase A and required the coexpression of a calcium channel beta subunit. In contrast, three neuronal non-L-type calcium channels, alpha(1A), alpha(1B) and alpha(1E), were not subject to voltage-dependent facilitation when coexpressed with a beta subuni t. The results indicate that the mechanism of neuronal L-type calcium channel facilitation involves the interaction of alpha(1) and beta sub units and is dependent on protein kinase A activity. The selective vol tage-dependent modulation of L-type calcium channels is likely to play an important role in neuronal physiology and plasticity